A novel hACE2 knock-in mouse model recapitulates pulmonary and intestinal SARS-CoV-2 infection

文献类型： 外文期刊

第一作者： Zhou, Xiaoyang

作者： Zhou, Xiaoyang;Zhang, Yu;Wang, Ruixuan;Xie, Peng;Zhu, Yunkai;Qiu, Minyue;Ding, Xiaoyan;Li, Jintao;Sun, Weiyang;Gao, Yuwei;Gu, Hongjing;Wang, Hui

作者机构：

关键词： mouse model; intestinal infection; SARS-CoV-2; immune cells; pneumonia

期刊名称：FRONTIERS IN MICROBIOLOGY （ 影响因子：5.2； 五年影响因子：6.2 ）

ISSN：

年卷期： 2023 年 14 卷

页码：

收录情况： SCI

摘要： Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is responsible for the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter the host, and the gastrointestinal tract is a potential infection site as this receptor is expressed on it. Multiple studies have indicated that an increasing number of COVID-19 patients presented with gastrointestinal symptoms that are highly associated with disease severity. Moreover, emerging evidence has demonstrated that alterations in the gut immune microenvironment induced by intestinal SARS-CoV-2 infection can regulate respiratory symptoms. Therefore, targeting the intestines may be a candidate therapeutic strategy in patients with COVID-19; however, no mouse model can serve as an appropriate infection model for the development of fatal pneumonia while mimicking intestinal infection. In this study, a novel human ACE2 knock-in (KI) mouse model (or hACE2-KI) was systemically compared with the popular K18-hACE2 mice; it showed differences in the distribution of lung and intestinal infections and pathophysiological characteristics. These newly generated hACE2-KI mice were susceptible to intranasal infection with SARS-CoV-2, and not only developed mild to severe lung injury, but also acquired intestinal infection. Consequently, this model can be a useful tool for studying intestinal SARS-CoV-2 infection and developing effective therapeutic strategies.

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